Studies will be made of the changes in whole mouse brain and in brain regions of the levels of metabolites, members of the citric acid cycle and others, induced by pyrithiamine-induced thiamine deficiency. The diet will be changed to obtain data relevant to the problem of thiamine-sparing by diets high in fat, and to study the problem of apparent carbohydrate toxicity in thiamine deficient mice. These studies will focus upon, but will not be restricted to cocarboxylase, acetyl-CoA, succinyl-Co-A, other short-chain acyl CoA's and total acid soluble CoA, assays for which have recently been developed in this laboratory. A method for measurement of flux through the pentose-P shunt will be developed and used in deficient animals. Regional studies of thiamine uptake by brain and of the distribution of thiamine diphosphatase in brain will be done. Bibliographic references: Seltzer, J.L. and McDougal, D.B.,Jr. (1974) Temporal changes of regional cocarboxylase levels in thiamine-depleted mouse brain. Am. J. Physiol. 227, 714-718.